A new approach to quantitation of the various sources of bilrubin in man.

Studies of the "early labeling" of fecal bile pigment have been widely interpreted as indicating that 10 to 20 per cent of total bile pigment production in normal man is derived from the processes which give rise to the "early labeled" pigment peak (ELP). However, this conclusion is based on a very small number of studies with inherent experimental and analytic limitations. In the present study, a new experimental approach was employed. Plasma bilirubin turnover (BRT), total red blood cell volume (TRCV), and red cell survival were measured in 26 normal volunteers and 35 patients with various hepatic and/or hematologic disorders. The quantity of bilirubin derived from red blood cell degradation (BRRBC) was calculated from TRCV and the mean red cell life-span, and the difference between BRT and BRRBC, designated "excess bilirubin synthesis (EBS)," was considered to represent the quantity of bilirubin derived from the processes responsible for ELP. In normal volunteer subjects, EBS averaged 1.0 mg. per kilogram per day, and accounted for 25 per cent of daily bilirubin turnover. Hence, results derived by this approach exceeded the range estimated from analysis of "early labeled peak" data. Further analysis of the data in terms of a simple model of bilirubin sources was compatible with the hypothesis that EBS consists of an essentially constant component, averaging 0.8 mg. per kilogram per day, presumably derived principally from the liver, and a second component which varies with the erthropoietic rate. Hence, in normal man the liver may contribute the major fraction of EBS.